ABSTRACT Crohn's disease (CD) is an autoimmune disease affecting 700,000 people in the United States. The pathology of CD is characterized by obstructing intestinal strictures due to inflammation, fibrosis, or a combination of both . The accurate characterization of the strictures is critical, as the inflammatory strictures can be treated medically, yet the fibrotic strictures are irreversible and have to be removed surgically.for characterizing the strictures is endoscopic biopsy, in which a small piece of The standard procedure tissue is removed for histopathology. Compared to the inflammatory strictures, the fibrotic strictures are characterized by the increased collagen content and the loss of stratified tissue architecture. Due to the limited number of sampling locations, comprehensive assessment of the strictures by endoscopic biopsy is hard to achieve. Monophysics imaging modalities such as ultrasound, magnetic resonance and X-ray imaging have demonstrated the capability of resolving the stratified architecture in the strictures. However, the primary diagnostic factor of CD is the change of histochemical components in the strictures (i.e. the collagen content). Optically (photo-) induced ultrasonic (-acoustic) imaging, namely photoacoustics imaging (PAI), is a multiphysics, non-ionizing and non-invasive imaging modality. PAI, unmatched by any imaging modality currently used for CD diagnosis, can resolve the microscopic distributions of individual histochemical components in biological tissue in vivo with optical sensitivity and ultrasonic resolution. The central hypothesis of this project is that the PAI can characterize intestinal strictures without tissue removal, by 1) quantifying the relative contents of histochemical components and 2) assessing the stratified tissue architecture in the strictures. The objective of this proposed project, by leveraging the research team?s expertise in PAI, endoscopic systems, animal models and clinical management of CD, is to develop a diagnostic strategy for characterizing the intestinal strictures in vivo based on PAI. Specific aims of this project include: 1) Characterize and optimize the performance of a prototype PAI probe in imaging intestinal strictures with rat model in situ and human specimens ex vivo, and 2) validate the proposed endoscopic PAI diagnostic strategy for intestinal strictures with rabbit model in vivo. The endoscopic PAI probe is in the shape of a small capsule extending through the instrument channel of an endoscope. Inside the capsule, a miniaturized 1-dimensional translation stage holds a focused transducer and fiber optics to formulate a B-scan (2-dimensional) PAI capability, providing diagnostic information comparable to histology. The proposedendoscopic PAI procedure fits seamlessly into the clinical endoscopy framework and is thereby highly translational. Once accomplished, the proposed diagnostic strategy, with unlimited sampling locations, will facilitate comprehensive assessment of the intestinal strictures to achieve in vivo biopsy, improving personalized therapeutic planning and the life quality for CD patients.